Dynamic Interpretation of Hedgehog Signaling in the Drosophila Wing Disc

Morphogens are classically defined as molecules that control patterning by acting at a distance to regulate gene expression in a concentration-dependent manner. In the Drosophila wing imaginal disc, secreted Hedgehog (Hh) forms an extracellular gradient that organizes patterning along the anterior–posterior axis and specifies at least three different domains of gene expression. Although the prevailing view is that Hh functions in the Drosophila wing disc as a classical morphogen, a direct correspondence between the borders of these patterns and Hh concentration thresholds has not been demonstrated. Here, we provide evidence that the interpretation of Hh signaling depends on the history of exposure to Hh and propose that a single concentration threshold is sufficient to support multiple outputs. Using mathematical modeling, we predict that at steady state, only two domains can be defined in response to Hh, suggesting that the boundaries of two or more gene expression patterns cannot be specified by a static Hh gradient. Computer simulations suggest that a spatial “overshoot” of the Hh gradient occurs, i.e., a transient state in which the Hh profile is expanded compared to the Hh steady-state gradient. Through a temporal examination of Hh target gene expression, we observe that the patterns initially expand anteriorly and then refine, providing in vivo evidence for the overshoot. The Hh gene network architecture suggests this overshoot results from the Hh-dependent up-regulation of the receptor, Patched (Ptc). In fact, when the network structure was altered such that the ptc gene is no longer up-regulated in response to Hh-signaling activation, we found that the patterns of gene expression, which have distinct borders in wild-type discs, now overlap. Our results support a model in which Hh gradient dynamics, resulting from Ptc up-regulation, play an instructional role in the establishment of patterns of gene expression

Molecular evolution of cyclin proteins in animals and fungi

<p>Abstract</p> <p>Background</p> <p>The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi.</p> <p>Results</p> <p>We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution.</p> <p>Conclusions</p> <p>The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.</p

On the Axiomatizability of Ready Traces, Ready Simulation, and Failure Traces

Fragments of mitochondrial DNA are known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear pseudogenes of the mtDNA. The insertion of a NUMT is a rare event. Hundreds of pseudogenes have been cataloged in the human genome. NUMTs are, in essence, a special type of mutation with their own internal timer, which is synchronized with an established molecular clock, the mtDNA. Thus insertion of NUMTs can be timed with respect to evolution milestones such as the emergence of new species. We asked whether NUMTs were inserted uniformly over time or preferentially during certain periods of evolution, as implied by the "punctuated evolution" model. To our surprise, the NUMT insertion times do appear nonrandom with at least one cluster positioned at around 2.8 million years ago (Ma). Interestingly, 2.8Ma closely corresponds to the time of emergence of the genus Homo, and to a well-documented period of major climate change ca. 2.9-2.5Ma. It is tempting to hypothesize that the insertion of NUMTs is related to the speciation process. NUMTs could be either "riders", i.e., their insertion could be facilitated by the overall higher genome rearrangement activity during speciation, or "drivers", i.e. they may more readily get fixed in the population due to positive selection associated with speciation. If correct, the hypothesis would support the idea that evolution of our genus may have happened in a rapid, punctuated manner

ОСОБЛИВОСТІ НОРМАТИВНО-ПРАВОВОГО РЕГУЛЮВАННЯ МОРАЛЬНО-ПСИХОЛОГІЧНОГО СТАНУ ВІЙСЬКОВОСЛУЖБОВЦІВ СЕКТОРУ БЕЗПЕКИ І ОБОРОНИ УКРАЇНИ

The process of building of the security and defense sector of Ukraine is accompanied by an integrated approach to strengthening the combat capability of military formations. The forms and methods of combat operations are changing, combat technology is becoming more and more complex, but a person remains the decisive part in performing military-combat tasks. At the same time, the critical importance in neutralizing and mitigating the impact of military threats on Ukraine's national security continues to depend on the high morale and psychological state of military personnel and the psychological readiness of the personnel of the security and defense sector of Ukraine to fulfill the tasks and their resilience to combat stress.For the successful accomplishment of the tasks, the forces of the security and defense sector of Ukraine should have a significant combat capability which includes the following main components: personnel, weapons, equipment, material resources. One of the most important is the servicemen, because only their successful activity ensures the reliable operation and use of weapons and military equipment. For qualitative performance of the set military and combat tasks, servicemen must have a set of necessary professional qualities, which in aggregate constitute a moral and psychological state.An analysis of modern legal and regulatory documents showed that there are different approaches to the content and structure of the concept of "moral and psychological state" of personnel and the difference in its evaluation and formation.The moral and psychological state of a serviceman is the current state of the human person's psyche, which is caused by the influence of the internal (professional qualities and individual psychological features of the person) and external (social, political, material and technical and natural) factors, which reflects his readiness to perform the service -battle tasks in the usual and extreme conditions, the components of which are the military-professional and psychological potentials of the serviceman.In our days, practical approaches to assessing the moral and psychological state as the most important component of the military potential of military formations are based on the use of appropriate methods, which are set out in the legal and regulatory documents of the forces of the security and defense sector of Ukraine. Проведено аналіз нормативно-правових документів, які регламентують порядок морально-психологічного забезпечення професійної діяльності сил сектору безпеки і оборони України. Визначено, що у документах є різні підходи до вибору категоріального апарату морально-психологічного стану особового складу і розбіжності у його оцінюванні, прогнозуванні та формуванні.

BioUniWA – WEB SERVICES GENERATION SYSTEM AND PIPELINES FOR UNIFIED ACCESS TO RESOURCES IN THE FIELD OF BIOINFORMATICS

We present the BioUniWA system for automatic generation of web services for unified access to resources in the field of bioinformatics. The BioUniWA system was originally designed as the BioInfoWF development system to support access to computing modules and pipelines through web services. BioUniWA can automatically generate web-based applications for computational modules and pipelines whose formal descriptions are defined by a language based on XML. In the future, one will be able to use these web-based applications in a variety of bioinformational systems, such as Taverna or Galaxy, as well as directly in the source code of applications to be developed. We have designed a tool that greatly simplifies the annotation of computing modules and schemes of pipelines, as well as their publication via Internet.BioUniWA is distributed under a free GNU general public license. The distribution package and user documentation are available at BioUniWA http://bioinfowf.bionet.nsc.ru

BioInfoWF – WEB SERVICES AND WEB INTERFACES GENERATOR FOR BIOINFORMATICS ANALYSIS

The BioinfoWF (Bioinformatics WorkFlow) system for automated generation of Web interface and Web services for bioinformatics programs. Each program module used in the system has metadescription in XML. The metadescriptions are used for automated generation of Web interface and Web services that can be used further in bioinformatics workflows. Computational modules can be organized in workflows. The tool we have developed significantly simplify the design and publication of modules for bioinformatics data analysis via the internet and their availability for scientific communities. The developed system makes is distributed under GNU GPL. The Source codes and documentation for BioinfoWF are available at http://bioinfowf.bionet.nsc.ru